Is AGBL5 p.Leu636= (c.1906T>C) pathogenic?

AGBL5 p.Leu636= (c.1906T>C) is classified Likely benign in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). Very rare (popmax 0.00305%, nfe).

How common is AGBL5 p.Leu636= (c.1906T>C) in the general population?

AGBL5 p.Leu636= (c.1906T>C) is very rare (popmax 0.00305%, nfe) (gnomAD).

AGBL5 p.Leu636=

c.1906T>C · rs777981614 · VCV1127035

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -4.7
Overall
CADD	3.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00305% European (non-Finnish) · 36/1,179,996 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.0026% 42/1,613,832 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,613
European (non-Finnish)grpmax	0.00305%	32,778
Admixed American	0.00167%	59,902
African / African-American	0.00134%	74,852

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AGBL5
Protein: p.Leu636=
Coding: c.1906T>C
MANE Select: NM_021831
dbSNP: rs777981614
Type: single nucleotide variant
Location: chr2:27059221 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 636: a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); a UniProt-annotated variant site (in rp75); the 'disordered' region

Full AGBL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGBL5 p.Arg220Ter Pathogenic ★★ same type
AGBL5 p.Arg487Ter Pathogenic ★★ same type
AGBL5 p.Trp592Ter Pathogenic ★★ same type
AGBL5 p.Tyr485Ter Pathogenic/Likely pathogenic ★★ same type
AGBL5 c.2355+4A>G Uncertain significance ★★ same type
AGBL5 c.551+5C>A Uncertain significance ★★ same type
AGBL5 p.Ala530Thr Uncertain significance ★★ ⚠ same type
AGBL5 p.Ala570Val Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/agbl5-p-leu636 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown